The coating of tablets is common in the pharmaceutical industry. Such coatings are applied for two main reasons: to achieve a desired cosmetic appearance, and, in some cases, to functionally introduce a substance such as an active pharmaceutical ingredient (API) to control drug release.
During the coating process, as the coating is added, several coating related properties change as coating is applied to the tablet in the coater. Such properties may include surface roughness, tablet gloss, and tablet temperature. The coating properties themselves, such as coating material concentration(s) and composition(s), tablet core composition, as well as the coater properties (i.e., spray rate, inlet temperature, drum speed, etc.) play a role in how these critical coating properties (values) change throughout the process, and what these values are at the end of the coating process.
For these properties, typically predefined limits are set to be reached or exceeded through the coating process. Such limits may depend upon tablet application, customs, type of product, and so forth. As such, it is critical that these properties be achieved before the tablets can be released to packaging. If one or more of the desired characteristics are not met, a batch of tablets may be rejected based upon poor coating quality, resulting in economic loss. Current practice in measuring surface roughness and tablet gloss is limited to off-line methods, typically at the end of the batch. If a small amount of sample is extracted (i.e., via a “thief”) during the batch, the measurement is done tablet-by-tablet in a relatively slow offline approach. The offline assay takes time and, if properties are not developing the way they should during the coating process, in a continuous manufacturing modality, the needed process changes cannot be done in a relatively “instantaneous” manner. With offline processes, the batch may be held in quarantine, for a period of time, as measurements are acquired before the batch can be “approved” and released. The extra steps cost time and money.
In addition, knowing the temperature of the tablet during the coating process can help eliminate possible temperature induced changes to components in the tablet that might be temperature sensitive including, for example, polymorphic changes in drug-loaded coatings. Temperature measurements, if acquired, could be difficult to measure of the individual tablets themselves, and would require the use of another sensor for this measurement—resulting in additional cost.
The current practice associated with measuring tablet gloss and roughness use off-line assay methods. For example, with surface roughness, an off-line laser profilometer is used on tablets removed from the coater, either during the batch or, more commonly, after the batch of tablets are coated. Other methods to test for surface roughness, such as SEM imaging EDX analysis and Terahertz pulsed imaging (TPI), can also be utilized offline. Another possible method to quantify surface roughness is the use of near infrared spectroscopy (NIR). The NIR method is based upon a diffuse reflectance signal, and the surface roughness, when measured off-line with the coated tablet set into a fixed geometry, could possibly be extracted from the coating signal.
As for tablet gloss, this coating property is commonly measured off-line with a gloss meter—a device that delivers a beam of light at a prescribed angle onto the tablet surface at a fixed intensity. The reflected intensity is measured at the equal but opposite angle. This method also requires that the tablet to be removed from the coater for the measurement, precluding an in situ, real-time measurement.
As for tablet temperature measurements, either during coating or during tablet discharge from the coater, the common practice is to monitor temperature via a thermocouple or non-contact infrared (IR) thermometer. For the latter, the IR thermometer laser beam must be focused only onto the tablets or else the measurement will be inaccurate since the tablets/tablet bed may be at a different temperature than surrounding surfaces, especially in continuous coaters.
Both surface roughness and tablet gloss have been examined with Raman in an imaging or mapping geometry via a Raman microscope format. However, this is currently done off-line on a per-tablet basis. Tablet temperature measurements may be carried out with an IR other device projected into the tablet bed. Coating temperature may also be measured using the coater inlet and outlet air temperatures, but a complex relationship could exist between such temperatures and tablet temperature. Temperature may be measured in pseudo-real-time, if individual tablets were removed at various intervals during the process. However, this is a “destructive” modality since tablets cannot be introduced back into the process once removed for measurement.